Gene expression profiling of the peripheral blood mononuclear cells of offspring of one type 2 diabetic parent
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Several lines of evidence from studies of both twins and offspring of people with type 2 diabetes have shown the importance of genetics in its pathogenesis. Impaired glucose tolerance (IGT) may reflect these genetic changes during the prediabetic stage. Thus, we performed a comprehensive analysis of the gene expression profiles of the peripheral blood mononuclear cells among offspring of one type 2 diabetic parent with normal glucose tolerance and impaired glucose tolerance in comparison to newly diagnosed diabetics and normal controls. Data were analysed from offspring of one type 2 diabetic parent. Gene expression profiles of 84 genes related to insulin-responsive genes were analysed using human insulin signalling pathway array. Of the 84 genes, 42 diabetic genes had at least a twofold change in expression for at least one comparison between the diabetic subjects, offspring with NGT and offspring with IGT as compared with controls. The most significant findings were that FOXP3 and SNAP25 were highly expressed in the offspring with IGT as compared with the controls, with a sixfold change in expression. The differential expression of the 42 genes among the offspring with IGT mainly demonstrates a defect in insulin secretion which suggests β cell dysfunction. The preponderance of experimental evidence favours the presence of impaired rather than excessive insulin secretion in the offspring before the development of IGT and thus supports the concept that the initial lesion in type 2 diabetes may involve impaired insulin secretion rather than insulin resistance. The results from our study suggest that β cell dysfunction starts early in the pathologic process and does not necessarily follow the stage of insulin resistance.
KeywordsType 2 diabetics Impaired glucose tolerance Normal glucose tolerance PBMCs FOXP3 SNAP25
The work of Karuthan Chinna was supported by University of Malaysia/Ministry of Higher Education (UM/MOHE) High Impact Research Grant E000010-20001. Language editing was provided by Barbara Every, ELS, of BioMedical Editor.
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